Variations in energy expenditure (EE) and substrate utilization were investigated in 12 surgical neonates (body weight, 2.81 +/- 0.15 kg) receiving total parenteral nutrition (TPN) at an energy intake of 66.34 +/- 2.16 kcal/kg/d in a thermoneutral environment of 32 degrees C to 34 degrees C. Respiratory gas exchange was continuously recorded for 12 hours by a computerized, open-circuit indirect calorimeter. Physical activity was monitored on a modified Freymond scale. Urine was collected over 3 days, including the time of the calorimetry study to determine the urinary nitrogen excretion rate. Oxygen consumption, carbon dioxide production, nonprotein respiratory quotient, and EE were calculated according to the principles of indirect calorimetry for each 30-minute period and for the entire 12 hours. During the indirect calorimetry study the patients were receiving a fat-free TPN mixture consisting of 10% glucose and 2% amino acids (GL/AA) for 8 hours. The fat-free TPN was interrupted by an isocaloric and isovolemic infusion of intralipid 10% (IL) for 4 hours. The effect of physical activity on EE was evaluated separately according to the macronutrient intake (GL/AA for 8 hours v IL for 4 hours) and then combined throughout the 12 hours of intravenous alimentation. The neonates were resting during 80% of the 12-hour study time (range, 38% to 90%). The partition of EE expressed as mean +/- SEM in kcal/kg/d was: total EE 48.5 +/- 2.1; resting EE 43.9 +/- 1.6; energy cost of activity 4.6 +/- 1.3.(ABSTRACT TRUNCATED AT 250 WORDS)